- Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate dehydrogenase
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Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.
- Zhu, Junsheng,Han, Le,Diao, Yanyan,Ren, Xiaoli,Xu, Minghao,Xu, Liuxin,Li, Shiliang,Li, Qiang,Dong, Dong,Huang, Jin,Liu, Xiaofeng,Zhao, Zhenjiang,Wang, Rui,Zhu, Lili,Xu, Yufang,Qian, Xuhong,Li, Honglin
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p. 1123 - 1139
(2015/03/04)
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- ISOINDOLINE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
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Provided herein are isoindoline compounds such as those of formula (I), pharmaceutical compositions comprising one or more of such compounds, and methods of their use for treating, preventing, or managing various diseases. Formula (I)
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Page/Page column 75-76
(2010/06/11)
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- Synthesis of some new 4-{2-[(aryl)amino]-1,3-thiazol-4-yl}benzene-1,2-diols as possible antibacterial and antifungal agents
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Some new 4-{2-[(aryl) amino]-1,3-thiazol-4-yl}benzene-1,2-diols are prepared and characterized by spectral analysis. The newly prepared compounds are studied for their antibacterial and antifungal activity. Interestingly, almost all the compounds are found to possess promising antibacterial and antifungal activity against all tested microorganisms. Copyright Taylor & Francis Group, LLC.
- Narayana,Ashalatha,Vijaya Raj,Suchetha Kumari
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p. 1381 - 1389
(2007/10/03)
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- Synthesis of some new 5-(2-substituted-1,3-thiazol-5-yl)-2-hydroxy benzamides and their 2-alkoxy derivatives as possible antifungal agents
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The 2-hydroxy-5-(1,3-thiazol-5-yl) benzamide (4a), 5-(2-amino-1, 3-thiazol-5-yl)-2-hydroxy benzamide (4b), 2-hydroxy-5-(2-alkyl-1,3-Thiazol-5-yl) benzamide (4c and 4d), 5-{2-[(N-substituted aryl)amino]-1,3-thiazol-5-yl}2- hydroxy benzamides (6a-j) were prepared by reacting 5-(bromoacetyl) salicylamide (2) with thiourea, thioformamide, thioalkylamide (3c-d) and substituted thioureas (5a-j) in absolute ethanol. These compounds were converted to 5-(2-substituted-1,3-thiazol-5-yl)-2-alkoxybenzamides and 5-(2-N-(substituted aryl)-1,3-thiazol-5-yl)-2-alkoxy benzamides (8a-g) by reacting with n-alkylbromides (7a-b) in presence of a base. The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral data. Compounds were also screened for their antifungal activity.
- Narayana,Vijaya Raj,Ashalatha,Kumari, N. Suchetha,Sarojini
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p. 867 - 872
(2007/10/03)
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- Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas
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An improved procedure for the preparation of arylthioureas consists of the reaction of benzoyl isothiocyanate with anilines in acetone and debenzoylation of the resultant N-aryl-N'-benzoylthioureas with 5percent aqueous sodium hydroxide.Bicycloalkylthioureas and N-(arylalkyl)thioureas (e.g. 9H-9-fluorenylthiourea) are directly prepared from the corresponding isothiocyanates and ammonia.
- Rasmussen, C. R.,Villani, F. J.,Weaner, L. E.,Reynolds, B. E.,Hood, A. R.,et al.
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p. 456 - 459
(2007/10/02)
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